# US 10,479,825 B2 · Antibody-mediated neutralization of Marburg virus

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- Number: US 10,479,825 B2
- Document ID: US10479825B2
- Status: Granted
- Kind: B2
- Application number: 15/553,311
- Filed: 2016-02-25
- Published: 2018-11-01
- Granted: 2019-11-19
- Earliest claimed: 2015-02-25
- Assignees: Vanderbilt University; Board of Regents, The University of Texas System
- Applicants: Vanderbilt University; The Board of Regents of the University of Texas System
- Inventors: James E. Crowe; Andrew I. Flyak; Alexander Bukreyev; Philipp Ilinykh
- Web page: https://patentgrep.com/patent/US10479825B2

## CPC

- C12Q 1/701: {Specific hybridization probes}
- A61P 31/14: for RNA viruses
- C07K 16/10: RNA viruses
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present disclosure is directed to antibodies binding to Marburg virus (MARV) glycoprotein (GP) and methods of use therefore.

## Claims

### Claim 1

An engineered cell producing an antibody or antibody fragment characterized by heavy chain CDR sequences of SEQ ID NOS: 104, 105 and 106 and light chain CDR sequences of SEQ ID NO: 150, DNN and SEQ ID NO: 151.

### Claim 2 (depends on 1)

The engineered cell of claim 1, wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences comprising SEQ ID NO: 25 and SEQ ID NO: 24, respectively.

### Claim 3 (depends on 1)

The engineered cell of claim 1, wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 90% identity to SEQ ID NO: 25 and SEQ ID NO: 24, respectively.

### Claim 4 (depends on 1)

The engineered cell of claim 1, wherein said antibody or antibody fragment comprises light and heavy chain variable sequences of SEQ ID NO: 61 and SEQ ID NO: 60, respectively.

### Claim 5 (depends on 1)

The engineered cell of claim 1, wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NO: 61 and SEQ ID NO: 60, respectively.

### Claim 6 (depends on 1)

The engineered cell of claim 1, wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab′)2 fragment, or Fv fragment.

### Claim 7 (depends on 1)

The engineered cell of claim 1, wherein said antibody is a chimeric antibody.

### Claim 8 (depends on 1)

The engineered cell of claim 1, wherein said antibody is an IgG.

### Claim 9 (depends on 1)

The engineered cell of claim 1, wherein said antibody or antibody fragment also binds to Ebola virus.

### Claim 10 (depends on 1)

The engineered cell of claim 1, wherein said antibody or antibody fragment further comprises a cell penetrating peptide or is an intrabody.

### Claim 11

A method of inhibiting a Marburg virus or Ebola virus in a subject comprising delivery to said subject an antibody or antibody fragment having heavy chain CDR sequences of SEQ ID NOS: 104, 105 and 106 and light chain CDR sequences of SEQ ID NO: 150, DNN and SEQ ID NO: 151.

### Claim 12 (depends on 11)

The method of claim 11, wherein said antibody or antibody fragment is a chimeric antibody or is bispecific antibody.

### Claim 13 (depends on 12)

The method of claim 12, wherein said antibody or antibody fragment is a bispecific antibody that (a) targets glycoprotein of a Marburg virus or Ebola virus, and (b) targets a structural feature of a Marburg or Ebola virus particle.

### Claim 14 (depends on 13)

The method of claim 13, wherein said structural feature is a Marburg or Ebola virus glycoprotein domain other than the receptor binding domain.

### Claim 15 (depends on 13)

The method of claim 13, wherein said structural feature is a Marburg or Ebola virus virion structure other than the glycoprotein.

### Claim 16 (depends on 15)

The method of claim 15, wherein said virion structure is a lipid, carbohydrate or protein.

### Claim 17 (depends on 11)

The method of claim 11, wherein said antibody or antibody fragment is a bispecific antibody that (a) targets a glycoprotein of a Marburg virus or Ebola virus particle and (b) targets a host cell surface structure cells that is trafficked to endosomes.

### Claim 18 (depends on 11)

The method of claim 11, wherein said subject is infected with a Marburg virus.

### Claim 19 (depends on 11)

The method of claim 11, wherein said subject is infected with an Ebola virus.

### Claim 20 (depends on 11)

The method of claim 11, wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences comprising SEQ ID NO: 25 and SEQ ID NO: 24, respectively.

### Claim 21 (depends on 11)

The engineered cell of claim 11, wherein said antibody or antibody fragment comprises light and heavy chain variable sequences of SEQ ID NO: 61 and SEQ ID NO: 60, respectively.

### Claim 22 (depends on 11)

The method of claim 11, wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.

### Claim 23 (depends on 11)

The method of claim 11, wherein said antibody is a chimeric antibody.

### Claim 24 (depends on 11)

The method of claim 11, wherein said antibody is an IgG.